Efficacy of flaxseed compared to ACE inhibition in treating anthracycline and trastuzumab induced cardiotoxicity

Abstract

BackgroundAlthough the current combination of surgery, radiation, and chemotherapy are used in the breast cancer setting, the administration of the anti-cancer drugs doxorubicin and trastuzumab is associated with an increased risk of developing heart failure. The aim of this study is to determine whether dietary flaxseed is comparable and/or synergistic with the angiotensin converting enzyme inhibitor perindopril in the treatment of doxorubicin and trastuzumab mediated cardiotoxicity. MethodsIn a chronic in vivo murine model (n=110), doxorubicin and trastuzumab (8mg/kg and 3mg/kg, respectively) were administered weekly for three weeks. Following this, the mice were randomized to daily consumption of a 10% flaxseed supplemented diet, administration of perindopril (3mg/kg) via oral gavage, or a combination of both flaxseed and perindopril for an additional three weeks. ResultsIn mice treated with doxorubicin and trastuzumab, the left ventricular ejection fraction (LVEF) decreased from 74±4% at baseline to 30±2% at week six. Treatment with either flaxseed, perindopril, or flaxseed and perindopril improved LVEF to 52±4%, 54±4%, and 55±3%, respectively (p<0.05). Although histological analyses confirmed significant loss of sarcomere integrity and vacuolization in the doxorubicin and trastuzumab treated mice, treatment with flaxseed, perindopril, or flaxseed and perindopril improved myocyte integrity. Finally, Bcl-2 interacting protein 3, high mobility group box 1 protein expression, and select oxylipins, were significantly elevated in mice receiving doxorubicin and trastuzumab; these markers were attenuated by treatment with either flaxseed, perindopril, or flaxseed and perindopril. ConclusionsFlaxseed was equivalent to perindopril at improving cardiovascular remodeling by reducing biomarkers of inflammation, mitochondrial damage, and cell death.